Natural Aristolactams and Aporphine Alkaloids as Inhibitors of CDK1/Cyclin B and DYRK1A

• Main Authors: Françoise Guéritte, Marc Litaudon, Laurent Meijer, Olivier Lozach, Vincent Dumontet, Séverine Amand, Bernard Bodo, Cécile Apel, Jessica Le Ven, Véronique Eparvier, Barbara Morleo, Guillaume Marti
• Format: Article
• Language: English
• Published: MDPI AG 2013-03-01
• Series: Molecules
• Subjects: Oxandra asbeckii; Goniothalamus dumontetii; Siparuna spp.; aporphinoids and aristolactams; kinases inhibitors
• Online Access: http://www.mdpi.com/1420-3049/18/3/3018

In an effort to find potent inhibitors of the protein kinases DYRK1A and CDK1/Cyclin B, a systematic in vitro evaluation of 2,500 plant extracts from New Caledonia and French Guyana was performed. Some extracts were found to strongly inhibit the activity of these kinases. Four aristolactams and one lignan were purified from the ethyl acetate extracts of Oxandra asbeckii and Goniothalamus dumontetii, and eleven aporphine alkaloids were isolated from the alkaloid extracts of Siparuna pachyantha, S. decipiens, S. guianensis and S. poeppigii. Among these compounds, velutinam, aristolactam AIIIA and medioresinol showed submicromolar IC50 values on DYRK1A.